P-Opioid receptor antagonist

Opioid systems in the brain are important for the reinforcing effects of ethanol. Selective p-opioid receptor antagonists reliably decrease ethanol drinking in rats. 

The biggest challenge is the treatment of addiction itself. Several approaches have been proposed, but all remain experimental. One approach is to pharmacologically reduce cravings. The P-opioid receptor antagonist and partial agonist naltrexone is FDA-approved for this indication in opioid and alcohol addiction. Its effect is modest and may involve a modulation of endogenous opioid systems. 

The extraordinary antinociceptive potency of the unknown compound was determined in a mouse model of acute nociception, the hot plate test. Despite the Straub-tail effect observed earlier, the antinociceptive effect of the compound could not be not antagonized with the p-opioid receptor antagonist naloxone but with the nAChR antagonist mecamylamine, so the unknown compound was deduced to be a potent nicotinic analgesic (Spande et al., 1992 Qian et al., 1993 Badio and Daly, 1994 Sullivan and Bannon, 1996). 

Somatostatin and its analogues have been reported to be OP3 (p) opioid receptor antagonists (40). Somatostatin infusions significantly reduced the effectiveness of morphine analgesia in a case report of three patients with... 

Cyprodime is a morphinan derivative, a (p) OPIOID RECEPTOR ANTAGONIST. 

Viscusi ER, Gan TJ, Leslie JB, Foss JF, Talon MD, Du W, Owens G (2009) Peripherally acting p-opioid receptor antagonists and postoperative ileus mechanisms of action and clinical applicability. Anesth Analg 108 1811-1822... 

Schmidhammer H, Burkard WP, Eggstein-Aeppli L, Smith CFC (1989) Synthesis and biological evaluation of 14-alkoxymorphinans. 2. (-)-N-(cyclopropylmethyl)-4, 14-dimethoxy-morphinan-6-one, a selective p opioid receptor antagonist. J Med Chem 32 418—421... 

Alcohol, Naltrexone is a p-opioid receptor antagonist first synthesized in the opioid 1960s. Naltrexone was approved by the FDA for the treatment of opioid addiction treatment in 1984 and alcohol addiction in 1994 [247]. Naltrexone blocks the euphoric effects of opioids by binding competitively to opioid receptors, but does little to curb craving for opioids. Because naltrexone is an opioid antagonist there is little risk of abuse or dependence given that it does not have intrinsic opiate effects and therefore is not reinforcing [248]. 

Another notable application of a-lithiation chemistiy was reported by Le Bourdonnec et al. in the synthesis of novel octahydro-lf/-pyrido[l,2-a]pyr-azines as p-opioid receptor antagonists. The key step in the synthesis of this core was an a-lithiation of an AI-Boc piperidine followed by carbo)q lation yielding a highly substituted piperidine in 73% yield (Scheme 11.39). ... 

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